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  • American Association for Cancer Research (AACR)  (4)
  • Troester, Melissa A.  (4)
  • 1
    In: Cancer Research Communications, American Association for Cancer Research (AACR), Vol. 2, No. 4 ( 2022-04-08), p. 211-219
    Abstract: Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P & lt; 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6). In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Our study suggests a limited role of gene–environment interactions in breast cancer risk.
    Type of Medium: Online Resource
    ISSN: 2767-9764
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 4 ( 2021-04-01), p. 623-642
    Abstract: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj & gt; 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)] , high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus & lt;20 years at first pregnancy [0.79 (0.72–0.86)]; & gt;0– & lt;5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)] ; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 3670-3670
    Abstract: Background: Studies have reported differences in associations between breast cancer risk factors and subtypes defined by hormone receptor status, particularly estrogen receptor (ER) positive versus ER negative tumors. Most studies have been conducted in women of European descent, and an expanding body of literature in other populations suggests differences by race/ethnicity. Clarifying whether associations between risk factors and disease subtypes are consistent across racial/ethnic populations has important implications for understanding disease etiology and for improving risk prediction models. To address this question, we conducted a qualitative literature review to investigate the consistency in associations between multiple breast cancer risk factors and risk of tumor subtypes in women of African, Asian, Hispanic, and European descent. Methods: We searched PubMed for publications between January 1, 1990 and June 8, 2021 that reported associations between breast cancer risk factors and risk of subtypes of the disease. We evaluated 19 risk factors, including reproductive, anthropometric, lifestyle, and diet factors, as well as medical history and use of menopausal hormone therapy (MHT). Subtypes were defined as ER positive or negative (specifically triple negative when available). We prioritized review studies (i.e., meta-analyses, systematic reviews, and pooled analyses) and included individual studies with populations not included in the reviews. The number of publications per risk factor ranged from 3 for calcium intake to 28 for parity, with up to 7 reviews per risk factor. Most publications reported estimates for women of European descent, followed by Asian, African, and Hispanic. Evidence of subtype heterogeneity was determined by expert review. Results: There was strong evidence of association between reproductive factors and MHT with risk of ER positive but not ER negative disease. Parity, younger age at first birth and older age at menarche were associated with lower risk of ER positive disease, while MHT use was associated with higher risk of ER positive disease. For these risk factors, we did not find evidence that risk associations or etiologic heterogeneity varied by race/ethnicity. For the other risk factors, there was limited or no evidence of heterogeneity in risk associations by subtype, which was consistent across racial/ethnic groups. Few publications, however, specifically studied women of non-European ancestry. Conclusion: For most breast cancer risk factors, evidence is insufficient to evaluate differences in ER-specific risk associations by race/ethnicity. More studies are needed to evaluate subtype-specific breast cancer risk factors in diverse populations, which will be important for informing the development of multi-ethnic/racial BC risk prediction models that account for subtype heterogeneity. Citation Format: Amber N. Hurson, Thomas U. Ahearn, Renske Keeman, Mustapha Abubakar, Audrey Y. Jung, Pooja Middha Kapoor, Hela Koka, Xiaohong R. Yang, Jenny Chang-Claude, Elena Martínez, Rulla M. Tamimi, Melissa A. Troester, Elisa V. Bandera, Marjanka K. Schmidt, Montserrat Garcia-Closas. Systematic literature review of risk factor associations with breast cancer subtypes in women of African, Asian, Hispanic, and European descents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3670.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 32, No. 12_Supplement ( 2023-12-01), p. B070-B070
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 32, No. 12_Supplement ( 2023-12-01), p. B070-B070
    Abstract: Background: Breast cancer subtyping has largely been based on immunohistochemical markers of estrogen receptor status. However, RNA-based intrinsic subtypes, including luminal (hormone receptor-positive) and non-luminal (hormone receptor-negative) have been shown to be etiologically relevant, with studies also suggesting other tumor markers (e.g., TP53 status) to be important contributors to etiologic heterogeneity. Compared to luminal tumors, non-luminal tumors are more likely to be TP53 mutant than wildtype-like. TP53 mutant breast cancers are associated with more aggressive tumor features and these mutations are more common among cases of African descent. However, few RNA-based subtyping studies have described etiologic heterogeneity in indigenous African populations. Therefore, we evaluated associations between established breast cancer risk factors and risk of PAM50 intrinsic subtypes and tumor subtypes defined by RNA-based TP53 functional status in the population-based Ghana Breast Health Study (GBHS). Methods: We analyzed data from 600 invasive breast cancer cases and 2,528 controls in the GBHS. RNA was extracted from formalin-fixed paraffin-embedded tumor samples and run on the nCounter® Breast Cancer 360™ Panel. Samples were then classified for intrinsic subtype (N=285 luminal, N=315 non-luminal) using a research version of the PAM50 assay and for TP53 functional status (N=333 wildtype-like, N=300 mutant-like) using a validated RNA signature. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for risk factors using polytomous logistic regression models adjusted for potential confounders. Results: About 1 in 4 tumors classified as ER-positive by immunohistochemistry were non-luminal by RNA expression. Similarly, about 1 in 5 ER-negative tumors were reclassified as luminal. Etiologic heterogeneity was observed by luminal subtype for certain reproductive factors. Higher parity (≥3 vs. & lt;3 births) was associated with lower risk of luminal tumors (OR [95% CI] = 0.68 [0.49, 0.92] ), but not with non-luminal tumors (0.95 [0.69, 1.30]). Likewise, later age at first birth (≥26 vs. & lt;19 years) was more strongly associated with risk of luminal than non-luminal tumors (2.16 [1.37, 3.40] and 1.30 [0.84, 2.00] , respectively). Consistent with previous findings, TP53 status was also an important etiologic factor and risk factor patterns mirrored those for luminal/non-luminal subtypes. Finally, we evaluated cross-classification of these two etiologic markers to identify risk factors that represent the dual action of both an estrogenic and a DNA-repair pathway. Age at first birth seems to suggest dual action. Conclusions: This study used high-quality RNA expression data to show that intrinsic subtype and TP53 status are useful breast tumor markers for describing etiologic heterogeneity, with cross-classification leading to improved understanding of the etiologic underpinnings of certain risk factors. This work has important implications for the use of gene-expression-based subtyping for breast cancer classification in this population. Citation Format: Amber N. Hurson, Ebonee N. Butler, Alina M. Hamilton, Bernard Petershie, Thomas U. Ahearn, Melissa A. Troester, Jonine Figueroa, Nicolas Titiloye, Montserrat Garcia-Closas, Mustapha Abubakar. Characterizing breast cancer etiologic subtypes in the Ghana Breast Health Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B070.
    Type of Medium: Online Resource
    ISSN: 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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